1

William Jordan

Senior Policy Advisor

Office of Pesticide Programs

Settlement Agreement 

in Litigation Against 

EPA’s Human Studies Rule 
2

Overview

 Litigation History

 Terms and Impacts of the 

Settlement Agreement

 Rulemaking Schedule
3

EPA’s 2006 Rule: ―Protections for 

Subjects in Human Research‖

 Promulgated in February 2006

 Modeled on the Common Rule

 Prohibits reliance on research involving intentional 

exposure of children and pregnant and nursing 

women 

 Requires review of protocols for proposed research 

by EPA & the HSRB

 . . . and more!
4

Legal Challenge

 Lawsuit filed against EPA in Spring 2006 by

 Natural Resources Defense Council, Inc.

 Pesticide Action Network of North America

 Pineros y Campesinos Unidos del Noroeste

 Physicians for Social Responsibility

 Farm Labor Organizing Committee of the AFL-CIO

 Migrant Clinicians Network

 Sen. Barbara Boxer, Sen. Bill Nelson, Rep. Henry 

Waxman, and Rep. Hilda Solis filed as amici curiae in 

support of petitioners
5

Petitioners’ Core Arguments

 The scope of the rule was inconsistent with the 

requirements of the 2006 Appropriations Act 

 The substance of the rule was inconsistent with 

 The principles proposed in the 2004 NAS report

 The principles of the Nuremberg Code 
6

Litigation Chronology

 Briefs and oral argument before U. S. Court of Appeals for 

the Second Circuit – Fall 2006 through January 2008

 Litigation stayed to permit settlement negotiations in April 

2009

 Settlement negotiations April 2009 through June 2010

 Settlement agreement filed June 18, 2010; available at: 

http://www.epa.gov/oppfead1/guidance/human-studiessettlement.pdf

 Litigation further stayed in June 2010 to allow 

implementation of the settlement agreement 
7

Settlement Agreement

 Defines schedule for proposed and final amendments 

to the 2006 rule 

 Attachment contains negotiated rule language to be 

proposed for public comment

 If EPA does not comply, petitioners’ recourse is to 

reopen lawsuit

 Negotiated amendments address petitioners’ core 

legal challenges:

 Scope to cover all EPA regulatory statutes

 Consistency with NAS recommendations

 Consistency with Nuremberg Code
8

Scope of the 2006 Rule

 2006 Rule applies to research—

 Involving intentional exposure of a human subject and 

 Intended for consideration under the pesticide laws 

(subparts K, L, M) or 

 relied on by EPA under the pesticide laws (subparts P & Q) 

 Petitioners’ concern: the 2006 rule text left a 

loophole for unethical human pesticide research to be 

conducted and submitted to EPA and relied on by 

EPA under other regulatory statutes, and thus to 

escape regulation
9

Proposed Scope Changes 

 Subpart K ―applies to all research initiated after [effective 

date of amended rule] involving intentional exposure of a 

human subject to a pesticide if . . . any person who 

conducted or supported such research intended . . . to 

submit results of the research to EPA for consideration in 

connection with any action that may be performed by EPA 

under any regulatory statute administered by EPA . . .‖

 Subparts L, M, and Q have similar changes 
10

Proposed Scope Changes (2)

 For research submitted/considered under FIFRA or FFDCA:

 Amended rule would apply to all 3rd-party research involving 

intentional exposure of a human subject

 Scope would not change from 2006 rule

 For research submitted/considered under any other EPA 

regulatory statutes: 

 Rule would apply to 3rd-party research involving intentional 

exposure of a human subject to a pesticide

 ―Pesticide‖ defined as in FIFRA—a substance or mixture intended 

for pesticidal effect

 Rule would not apply to research with multi-use chemicals (like 

formaldehyde or sulfur) unless they are tested as a pesticide 
11

Impact of Scope Changes

 EPA expects very little impact

 EPA has seen no study ―involving intentional 

exposure of a human subject to a pesticide‖ 

that was not covered by the 2006 rule
12

Consistency with NAS Principles

 The 2006 rule follows the NAS recommendation to 

start from the Common Rule to protect subjects of 

3rd-party research involving intentional exposure

 The 2006 rule does not include rule text specific to 

most of the 17 NAS recommendations 

 Petitioners’ concern: the 2006 rule does not 

require EPA to follow the NAS recommendations
13

Proposed Changes: Science

 EPA will propose to list in subpart P scientific issues 

that the Agency must address when reviewing 

proposed research:

 Need for human research involving intentional exposure

 Appropriateness of research design

 Representativeness of study participants

 Statistical adequacy of study design

 Good clinical practice guidelines and safety monitoring, 

if applicable
14

Proposed Changes: Ethics

EPA must consider in protocol review:

 Adequacy of previous animal 

studies

 Adequate identification and 

minimization of subject risks

 Appropriate balance of risks 

& benefits

 Equitable subject selection

 Free & fully informed 

consent

 IRB review and approval 

 Adequate protection for 

potentially vulnerable subjects

 Adequate protection for 

potentially sensitive subjects

 Appropriate and non-coercive 

payments to subjects 

 Provision of medical care for 

research-related injuries
15

Consistency with Nuremberg Code

 Like the Common Rule, EPA’s 2006 rule allows a ―legally 

authorized representative‖ to consent on behalf of a test 

subject who lacks capacity to provide informed consent

 Petitioners argue this provision is inconsistent with the 

Nuremberg Code (1947) which states: 

―The voluntary consent of the human subject is absolutely 

essential. This means that the person involved should have legal 

capacity to give consent . . . .‖
16

Changes Re: Surrogate Consent

 EPA will propose to delete from the 2006 rule 

all references to the provision of informed 

consent by a ―legally authorized 

representative‖

 EPA expects this change to have negligible 

impact
17

New Provisions Affecting HSRB

 § 26.1606 Human Studies Review Board review of 

proposed human research. In commenting on proposals for 

new research submitted to it by EPA, the Human Studies Review 

Board shall consider the scientific merits and ethical aspects of 

the proposed research, including all elements listed in section 

26.1603(b) and (c) and any additional conditions recommended 

pursuant to sec. 26.1603(d).

 § 26.1607 Human Studies Review Board review of 

completed human research. In commenting on reports of 

completed research submitted to it by EPA, the Human Studies 

Review Board shall consider the scientific merits and ethical 

aspects of the completed research, and shall apply the 

appropriate standards in Subpart Q. 
18

New Acceptance Standards

 EPA will propose to revise the 

substantive standards for relying on 

covered, completed research:

 Adding a categorical prohibition against 

reliance on ―scientifically invalid research‖ 

or data that are not ―relevant to a scientific 

or policy question important for EPA 

decision-making‖ 
19

Revised Acceptance Standards

 EPA will propose to change §26.1704:

EPA shall not rely on research ―if there is clear and convincing 

evidence that the conduct of the research was fundamentally 

unethical (e.g., the research was intended to seriously harm 

participants or failed to obtain informed consent), or was deficient 

relative to the ethical standards prevailing at the time the research 

was conducted in a way that placed participants at increased risk 

of harm (based on knowledge available at the time the study was 

conducted) or impaired their informed consent.‖

 EPA will propose parallel changes to §26.1705
20

Impact of Changes to Subparts P & Q

 EPA expects no impacts on third parties or on 

the HSRB

 EPA expects to add further detail to its 

scientific and ethical reviews of proposed and 

completed research to address specifically the 

elements that would be required by the 

proposed amendments
21

Final Points

 These changes would only apply prospectively

 EPA plans to propose a few additional changes 

to correct minor errors in the 2006 rule, and 

may propose other changes that would not 

affect third parties, EPA or the HSRB 

substantively, such as adding references to 

guidance documents or revising the organization 

of the rule
22

Rulemaking Schedule

 Proposed rule – signed by January 18, 

2011, and published for public comment

 Final rule – signed by December 18, 

2011

 The 2006 rule will remain in effect until 

it is replaced by a new final rule